Combination of cyclophosphamide and double-stranded DNA demonstrates synergistic toxicity against established xenografts

Cancer Cell International
Ekaterina A AlyamkinaMikhail A Shurdov

Abstract

Extracellular double-stranded DNA participates in various processes in an organism. Here we report the suppressive effects of fragmented human double-stranded DNA along or in combination with cyclophosphamide on solid and ascites grafts of mouse Krebs-2 tumor cells and DNA preparation on human breast adenocarcinoma cell line MCF-7. Apoptosis and necrosis were assayed by electrophoretic analysis (DNA nucleosomal fragmentation) and by measurements of LDH levels in ascitic fluid, respectively. DNA internalization into MCF-7 was analyzed by flow cytometry and fluorescence microscopy. Direct cytotoxic activity of double-stranded DNA (along or in combination with cyclophosphamide) on a solid transplant was demonstrated. This resulted in delayed solid tumor proliferation and partial tumor lysis due to necrosis of the tumor and adjacent tissues. In the case of ascites form of tumor, extensive apoptosis and secondary necrosis were observed. Similarly, MCF-7 cells showed induction of massive apoptosis (up to 45%) as a result of treatments with double-stranded DNA preparation. Double-stranded DNA (along or in combination with cyclophosphamide) induces massive apoptosis of Krebs-2 ascite cells and MCF-7 cell line (DNA only). In treated mic...Continue Reading

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Citations

Jun 23, 2018·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Tamara TyrinovaElena Chernykh
Feb 13, 2016·Oncotarget·Ekaterina A PotterSergey S Bogachev
Dec 19, 2019·Acta Neuropathologica·Viktoria MelcherKornelius Kerl

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Datasets Mentioned

BETA
AC002400.1

Methods Mentioned

BETA
fluorescence microscopy
electrophoresis
PCR
flow

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Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

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